The proposed studies were designed to fulfill two major specific aims, i.e. (1) to determine whether laboratory contact with murine mammary tumor virus (MuMTV) results in specific immune responses in humans, and (2) to determine whether breast cancer patients develop similar immune responses. To accomplish these goals, immune responses in four distinct human populations will be examined: (1) men and women with low and high contact exposure to MuMTV; (2) patients with benign mastopathies; (3) breast cancer patients; and (4) disease-free individuals, age- and sex-matched with regard to the first three populations without laboratory contact with MuMTV. To investigate specific humoral immune responses, human sera are reacted with nitrocellulose filter strips containing adsorbed MuMTV proteins following electrophoretic separation, allowing a rapid assessment of antibody class as well as identifying the pertinent MuMTV antigen(s). Corroborative evidence will be obtained with cellular immunofluorescence assays. Cell-mediated immune responses will be monitored by the lymphocyte migration inhibition assay. Our preliminary results strongly indicate that laboratory exposure to MuMTV induces specific humoral responses to MuMTV antigens (mainly gp55, gp34 and p37 and p28) with greater frequency and higher titers in women as compared to men; these responses are uncommon in age- and sex-matched controls. Breast cancer patients also have a high frequency of antibody responses to MuMTV antigens. The proposed studies, based on these preliminary data, will aid in establishing a sound basis for human immune responses to MuMTV, a type-B RNA tumor virus, which has not been reliably observed with type-C viruses. These results will be especially pertinent for breast cancer patients because it should establish that these individuals have had greater contact with MuMTV either by exogenous exposure and/or activation of an endogenous, MuMTV-related virus or antigens.